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If
you or someone in your family has Alzheimer's disease,
relatives have a higher risk than the general population
for developing the disease. In fact people with at least
one first-degree relative (parent or sibling) with Alzheimer's
disease are 3.5 times as likely to develop the disease.
This risk increases for each additional relative with
Alzheimer's disease. This strong tendency of Alzheimer's
disease to run in families is due, in part, to mutations
in certain genes. Scientists have found several genes that are involved in early onset Alzheimer's disease, but so far they do not know the gene responsible for inherited late-onset Alzheimer's disease. (For recent news about late onset Alzheimer's genes, see Related News below.)

Genetics of Early Onset Alzheimer's Disease

About
five percent of all Alzheimer's disease is caused
by a mutation in one of three genes.

About
five percent of all Alzheimer's disease is caused by a
mutation in one of three genes, called APP, presenilin
1 (PS1), and presenilin 2 (PS2). Each of these genes is inherited in a dominant
fashion. This means that it is only necessary to inherit
one mutated copy of the gene in order to develop Alzheimer's
disease. Those who do inherit a mutated form of these
genes tend to develop Alzheimer's disease early in life
(younger than age 65) and have a strong family history
of the disease.

The
APP Gene

A
mutation in the gene that makes APP is believed
to be responsible for 5 to 20 percent of all early
onset familial Alzheimer's disease.

In
people with Alzheimer's disease, deposits called amyloid
plaques build up in the brain. These are composed, in
part, of a protein called beta-amyloid, which is a fragment
of the amyloid precursor protein (APP). A mutation in
the gene that makes APP is believed to be responsible
for 5 to 20 percent of all early onset familial Alzheimer's
disease. People with a mutation in the APP gene tend
to develop Alzheimer's disease at around age 50.

So
far, researchers have found six different mutations
in the APP gene, the most common of which has been identified
as the cause of Alzheimer's in 16 families of European
and Japanese descent. Each of the other five mutations
has only been found to cause Alzheimer's diseaes in
a single family. Although each mutation is different,
they all occur in the same region of the gene. This
tells researchers that this gene region is important
in order to make an APP that functions normally.

The
PS1 Gene

Mutations
in a gene called PS1 account for about half of all
early onset Alzheimer's disease in families.

Mutations
in a gene called PS1 account for about half of all early
onset Alzheimer's disease in families. Despite its importance
in the disease, researchers do not know what role PS1
normally plays in the body.

Researchers
have found more than 40 different mutations in the PS1
gene that cause early onset Alzheimer's
disease in families of different ethnic backgrounds.

People
with mutations in PS1 develop Alzheimer's disease
at the earliest age.

People
with mutations in PS1 develop Alzheimer's disease at
the earliest age, ranging from 29 to 62 but with an
average age of 44 years. Families with a particular
PS1 mutation tend to develop Alzheimer's at the same
age.

In
four families with mutations in PS1, those who develop
Alzheimer's disease also have weakness in the legs and
more extensive changes in their brains than most people
with Alzheimer's disease.

The
PS2 Gene

Mutations
in PS2 have only been found in six different families.

The
PS2 gene has a very similar sequence to the PS1 gene,
and, like the PS1 gene, researchers do not know its
normal role in the body. Mutations in the PS2 gene are
very rare. In fact, mutations in this gene have only
been found in six different families with Alzheimer's
disease. One mutation accounts for Alzheimer's disease
in five German families and the other is responsible
for the disease in an Italian family.

Unlike
the PS2 or APP genes, researchers have found people
who have a mutation in the PS2 gene but did not develop
Alzheimer's disease. This, and the longer duration of
Alzheimer's disease in people with PS2 mutations, makes
researchers think that mutations in PS2 cause a less
aggressive form of Alzheimer's than in people with PS1
mutations. The age when people with PS2 mutation develop
symptoms of Alzheimer's disease varies even in the same
family, indicating that some environmental factors also
influence when a person with a PS2 mutation develops
the disease.

Alzheimer's
Susceptibility Genes

Not
all people who inherit the E4 version of APOE will
develop Alzheimer's disease, and not all people
with Alzheimer's disease have this version of the
gene.

People
who inherit mutated APP, PS1, or PS2 genes are very
likely to develop Alzheimer's disease at some point
in their lives. These genes are considered predictive.
However, other genes also exist that only influence
a person's susceptibility to Alzheimer's disease, but
do not mean that a person is more likely than not to
develop the disease. The best studied of these is apolipoprotein
E (APOE). APOE has functions throughout the body: transporting
cholesterol, regulating the immune system,
aiding in nerve regeneration, and metabolism.

There
are four different forms of the APOE gene. Inheriting
one of these forms  called E4  increases
a person's risk of developing Alzheimer's disease by
three-fold. Inheriting two E4 copies of the gene increases
risk by 12- to 15-fold. People with two copies of E4
also tend to develop Alzheimer's disease earlier in
life than the general population. The E4 version of
APOE is present in about 15 percent of all Caucasian
people and is even more common in people of African
descent. However, not all of these people develop Alzheimer's
disease, and not all people who have Alzheimer's disease
also have the E4 version of APOE. This means that other
environmental or genetic factors are also required in
order for a person to develop Alzheimer's. Genetic
testing for the APOE gene is
not recommended for healthy people. However, it may
be a useful diagnostic test in someone with dementia.